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Dr.
Meryl Nass
September
10, 2000
Presented at the International
Public Conference on Vaccination 2000
Anthrax vaccine was licensed by the Division of Biologic Standards
at the National Institutes of Health in 1970, using limited safety
data and efficacy data obtained in large part from a different anthrax
vaccine.
The FDA began licensing vaccines several years later and at
the time anthrax was licensed there was no
requirement for demonstrating efficacy in humans. The
vaccine was approved for two limited markets, workers exposed to
imported animal products, and lab investigators using anthrax. Efficacy
was demonstrated for cutaneous anthrax but not for inhalation anthrax
in the studies. By the way, you don’t need to use a vaccine
for cutaneous anthrax as it is not a fatal disease and is easily
treated with antibiotics.
This 1960 paper by Brachman et al used a different, earlier
vaccine, but this is the only efficacy study
of an anthrax vaccine ever published, and has been used subsequently
to justify vaccine effectiveness.
A New Hampshire goat hair mill had nine anthrax cases in persons
who were not vaccinated. But only ¼ of the mill workers had
received the vaccine, and it was found that the vaccinated workers
worked in areas of the plant where there were lower spore counts,
so they were at lower risk for anthrax than the placebo group.
Two years later the same authors published another evaluation of
the vaccine using the same study population but this time included
three additional mills. There were a total of 26 cases of anthrax
at the four mills during the study. Five cases occurred in persons
who had received some doses of vaccine and fifteen cases in persons
who received placebo vaccine. Six cases occurred in workers who
chose not to participate in the study.
However, the authors now reported that the vaccine was highly
effective, and in performing the statistical analysis, they threw
out four of the five anthrax cases in vaccinated workers for not
having received enough doses of vaccine, to calculate a vaccine
effectiveness of 92.5%, rather than an effectiveness of about 65%,
had they included the other four cases. This 92.5% statistic, fallacious
back in 1962, and generated by an older vaccine, has been used ever
since to justify the anthrax vaccine program.
This is a table from the 1960's CDC observational study of the
current vaccine, which was required to demonstrate safety so the
vaccine could be licensed. There are several interesting things
about this study. First, the investigators performed active surveillance
for local vaccine reactions only, at 24 and 48 hours after giving
the vaccine. They were careful to record local reactions, but paid
only cursory attention to systemic reactions, and did not perform
active surveillance for systemic reactions. In fact, at one mill
a large number of systemic reactions were reported, but this was
blamed on an over zealous nurse.
The physician working at that mill pointed out that the reaction
rate was no greater than with other vaccines such as typhoid. No
one noticed that typhoid was the most reactogenic vaccine in use
then. Also, notice that the reaction rates are highly variable from
one series to the other, which may suggest a large difference between
the lots, or a major difference in the recording of the effects
by the observers. Note also that they used both the old vaccine,
used in the earlier trial, and the current anthrax vaccine, despite
the fact that the old vaccine was 16 years old at the time the study
was done.
Over the next 20 years, from 1970 to 1990, only a small number
of persons were vaccinated with this vaccine: between 200 and 2,000,
according to Dr. Kwai Chan's GAO report to Congress. "In our
discussion with scientists at Fort Dietrich, the estimates of number
of people who may have received this vaccine over a 30 years period
range from somewhere between 200 to about 2,000 at the most. And
we don’t know who those individuals are. There has been no
follow up ... " Vaccine recipients were never studied systematically
and as far an anyone knew the vaccine was safe.
In 1985 the FDA was reviewing a number of products that had been
licensed prior to the more stringent regulations, and anthrax vaccine
was reviewed by an expert panel. FDA concluded, "Immunization
with this vaccine is indicated only for certain occupational groups
with risk of uncontrollable or unavoidable exposure to the organism".
They also pointed out that "Inhalation anthrax occurred too
infrequently to assess the protective effect of vaccine against
this form of the disease." Despite these qualifications the
decision to vaccinate US troops against anthrax was made as we developed
Operation Desert Shield and Operation Desert Storm.
A number of things were not taken into account then, and have yet
to be taken into account, although 2.5 million military service
members: active, reserve and Coast Guard are in the pipeline to
be vaccinated, with 450,000 having already begun the series.
What was not considered when the decision to vaccinate troops
against anthrax was made?
- First, long-term safety of the vaccine has never been established.
- Second, the old efficacy rate was fallacious and came from
an older vaccine -- no one knew how effective this newer vaccine
would be.
- Third, the stockpile was old and many lots had expired but been
re-dated, as if they were new, with only a retest of potency.
- Fourth, the lots were extremely heterogeneous, with variable
side effects and potency.
- Fifth, the manufacturer was far out of compliance with good
manufacturing practices, and had never had its anthrax line properly
inspected. Sixth, use for prophylaxis against biological warfare
was not an FDA approved indication.
Even if the efficacy rate for this vaccine in mill workers were
known, it would probably bear very little relationship to efficacy
in a bio warfare setting, where spore counts would be much higher
and anthrax strains would be specially selected for virulence. The
fact that genetically engineered anthrax had been shown to evade
vaccine protection was ignored. Monkey data were cited but guinea
pig data, which showed very poor efficacy against virulent strains,
was ignored.
Although the stockpile was old there was no FDA approved standard
operating procedure for re-using expired lots, and no retesting
for degradents, preservatives or sterility took place before approving
the use of expired vaccine. It is now known that the potency test
is unreliable and unreproducible. Finally, there had never been
a protocol added to the vaccine license, which was required before
reusing expired vaccine, yet FDA had permitted the manufacturer
to continually redate old vaccine stocks since 1970.
This appears to have been no aberration. The military had a policy
of storing vaccines for very long periods. In fact, they knew that
if licensed vaccines were stored in bulk rather than in small
vials they would legally last indefinitely, and if they were
investigational vaccines they would never
expire, no matter how stored, according to FDA regulations.
It turned out that some lots were 40 times as potent as other lots.
The manufacturing process had never been required to demonstrate
lot-to-lot product consistency, although that is part of FDA’s
normal requirement for vaccines. The result is that studies performed
on one lot might not be applicable to other lots, and that problems
and side effects from one lot could not be predicted from studies
on a different lot.
Although FDA was legally required to inspect the anthrax portion
of the manufacturing plant every two years, it did not fulfill this
obligation, and appears to have allowed the Army to perform its
own inspections. When FDA finally went in and did a thorough inspection
one month before the current vaccine program began, they found so
many problems that they immediately quarantined 11 lots of vaccine,
and the manufacturer "voluntarily" shut down for major
repairs and renovations. Although those renovations have since been
completed, the FDA has not allowed the manufacturer to reopen, and
new lots of vaccine that have been made in the last 15 months remain
under quarantine.
Because prophylaxis against biological warfare was not an FDA approved
indication for the vaccine, such use both during the Gulf War and
presently should only have been conducted using an investigational
new drug protocol. This would have required the informed consent
of vaccine recipients. The Defense Department actually did obtain
an IND for adding inhalation to the vaccine indications in 1996.
Although they claim it does not affect the current use, the IND's
existence opens up an interesting legal question of whether troops
receiving vaccine to protect against inhalation anthrax should be
covered by IND protection. This will likely be resolved in the courts.
After the vaccine was used on 150,000 US troops in the Gulf War
one would expect that we would now have a good idea about safety
of the vaccine. However, that is not the case. The very large question
of whether Gulf War Illness is related to anthrax vaccination has
not yet been resolved. Why is that?
Although the Defense Department and Veteran’s Administration
have spent over 150 million dollars sponsoring over 120
studies of Gulf War Illness, not a
single one of these studies in the United States has examined
the relationship between anthrax vaccine and Gulf War Illness,
although sixteen other Gulf War exposures have been studied. Instead
the Defense Department has used a different strategy. A number of
expert scientific panels were convened between 1994 and 1996. They
were asked to comment on whether anthrax and botulinum toxoid vaccines
could perhaps contribute to Gulf War Illness. None of the panels
presented here, with the exception of the Presidential Advisory
Committee, cited any references.
In the absence of data they drew the following conclusions: The
NIH Technology Assessment Workshop said, "no long term adverse
effects have been documented". The VA said "both vaccines,
anthrax and botulinum toxoid have been used for many years without
adverse effects. All three review panels, The Institute of Medicine,
Presidential Advisory Committee and the Defense Science Board Review
panels all stated that no long-term adverse effects have been documented
or would be expected. Further study of the potential adverse effects
of vaccines in this population is not recommended by any of the
three panels nor is it endorsed in this plan."
The Presidential Advisory Committee produced a series of final
reports as further information about Gulf War exposures continued
to come to light. In 1996 they said, "The Committee concludes
it is unlikely that health effects reported by Gulf War Veterans
today are the result of exposure to the botulinum toxoid or anthrax
vaccines, used alone or in combination". They cited five references
for this claim, all of which were to Defense Department briefers.
The Institute of Medicine said, "The Committee knows of no
evidence of any chronic effect." The Defense Department attempted
to sidestep any actual study of anthrax vaccine and Gulf War veterans’
illnesses. They said it was impossible
to do a study because the Gulf War vaccination records
have all been lost.
However, the document cited here indicates that the Gulf War vaccine
records had actually been classified rather than lost. It says "All
original records and documents used in identifying units and personnel
immunized during Operation Desert Storm are still considered classified
information." But Dr. Philip Pittman at Fort Detrick studied
the effect of booster doses of anthrax and botulinum toxoid vaccines
several years after the Gulf War. To do this, he was able to identify
400 service members at Fort Bragg who had received anthrax and botulinum
vaccinations during the Gulf War. Somehow, the names of vaccine
recipients, the dates of vaccination and the numbers of doses for
all 400 participants at Fort Bragg were found.
The results of his study were interesting. They showed that systemic
reactions occurred in 44% of the recipients of vaccine.
However, subjects received botulinum vaccine in one arm and anthrax
in the other, so it is uncertain how many of these reactions are
due to the anthrax vaccine alone. This study also showed that after
30 days, 3% of the subjects continued to have adverse systemic reactions.
Whether their problems resolved is unknown. This appears to be an
unprecedented rate of long term reactions, but it was ignored.
What then can be said about Gulf War Illness and anthrax vaccination?
There has only been one study done and it was performed in England
on service members who had received the British anthrax vaccine,
which is similar but not identical to the one used on US troops.
This study was published in the Lancet in January of 1999 and the
authors wrote, "vaccination against biological warfare and
multiple routine vaccinations were associated with this CDC multi-symptom
syndrome, (which is a definition of Gulf War Syndrome) in the Gulf
War cohort". An accompanying commentary, written by Dr. Stephen
Straus of the NIH, said "vaccination against plague and
anthrax before deployment to the Gulf correlated highly
with illness.
The investigators speculate that these vaccines more so than the
routine ones given to service personnel had unanticipated effects."
Therefore we do not yet know conclusively whether anthrax vaccine
caused or contributed to the development of Gulf War Illness, but
we suspect it. Further evidence comes from the large number of gulf
era service members who received anthrax vaccine, but were never
sent to the Gulf, and subsequently developed typical Gulf War Illnesses.
They all received more than one vaccination so we can’t say
which has caused their illness, but they had no other Gulf exposures,
so the vaccine connection is very significant.
Despite all these unanswered questions, the decision was made to
begin vaccinating all US service members against anthrax in early
1998. And not only anthrax: vaccines against a number of other biological
warfare threat agents are in development. Recently the military's
Joint Vaccine Acquisition Program, the umbrella program under which
all these vaccines will be developed, has talked about a total of
40-50 new vaccines for all service members. This program was initially
funded in 1997 by Congress with 322 million dollars, and it has
subsequently received additional appropriations.
There might be a relationship between the military’s interest
in vaccinating troops, and the pharmaceutical industry's interest
in vaccinating civilians. After passage of a Federal law in
1986, which made vaccine manufacturers no longer liable for adverse
effects unless there was a production error, the financial climate
for vaccine manufacturers started to improve. Furthermore, advances
in genetic engineering made it much easier to create new antigens
and microorganisms for vaccines. It is conceivable that the military
vaccine program will be developing new techniques and possibly new
vaccine adjuvants that will be tested on the military population
and used later in civilian vaccines.
I'd like to speak briefly about reporting and reviewing adverse
events. The anthrax vaccine program began vaccinating service members
in March of 1998. In eleven months 550,000 vaccine doses had been
administered but only 39 VAERS (Vaccine Adverse Effects Reporting
System) reports had been filed with the FDA. When Congressman Shays
asked the Defense Department about the vaccine program, because
of the large number of reports of serious illnesses that had reached
Congress, he was presented with this slide and was told that the
total adverse reaction rate was only .007%, and that anthrax vaccine
was safer than childhood vaccines. What DOD did was to take the
total number of reports to FDA of adverse effects and call it the
sum total of all adverse events.
However, it turned out that the military had instituted a policy
to limit the reports of adverse events before the first vaccination
was ever given! Although normally physicians and vaccine recipients
are encouraged to report to FDA any adverse reaction they choose,
military medical personnel were told that
only adverse reactions which resulted in hospitalization,
or more than 24 hours of lost duty time could be reported to FDA.
This kept the reporting rates remarkably
low. When the difficulties in reporting adverse effects
to FDA were reported in Congressional testimony in July 1999, the
policy immediately changed. There are now about 1500 reports of
adverse reactions to anthrax vaccine received by FDA, and approximately
one in every three hundred vaccine recipients has officially reported
an adverse reaction, despite continuing stories of obstructions
being placed in the way of reporting.
What kinds of reactions are being seen? Data from a study conducted
by Dr. Pittman in 1998 on Seventh Day Adventists who had served
as human guinea pigs at Fort Detrick in the 1960’s and the
1970’s. Many of these people received anthrax vaccine and had
never been followed up. However, 25 years after the program, named
"Operation White Coat" ended, all the alumni were invited
back to Fort Detrick for a weekend of fellowship, and asked to participate
in the following study. What questions were asked regarding their
symptoms?
The following list of twelve symptoms was given to each participant
and they were asked to comment on frequency and severity. Please
note that all of these symptoms are what is seen in Gulf War Illness,
and now these are the chronic symptoms most commonly seen in those
reporting problems after anthrax vaccination. While I'm on this
subject, vaccine recipients also report a variety of neurologic
disorders, especially tremors, and endrocrine disorders. We suspect
these to have an autoimmune basis. A recent autopsy of a vaccine
recipient showed death to be due to coronary artery vasculitis,
or what appears to be a series of heart attacks occurring shortly
after vaccination, and due to autoimmunity.
With 1500 VAERS filed why hasn’t FDA stopped the program?
Well, this is one page from a list of the VAERS reports received
by FDA that I got through the Freedom on Information Act. This report
lists seven people who have filed adverse event reports. You can
see that it is extremely difficult to tell what the severity of
the symptoms is and what the duration is. Two of these people report
severe fatigue but fatigue is a very subjective symptom. The FDA
has not paid it a lot of attention, although chronic fatigue syndrome
and fibromyalgia are commonly seen in both Gulf War Illness and
the post anthrax vaccine syndrome. FDA has its own list of terms
that are used to describe adverse reactions.
The system is called COSTART and the terms that are used, tend
to confuse, rather than illuminate the adverse reactions. For instance,
the term asthenia, used twice on this page, is one that has been
out of use for a century. The term " Immune system disorder,"
is not specific enough to be useful, and thus likely to be ignored.
I have reviewed hundreds of these VAERS reports and it is my belief
that this system makes it impossible to tell whether different people
are reporting the same types of illnesses, and it is therefore impossible
to tell whether their reactions are due to the vaccine.
The VAERS reports are received by a private company working as
a contractor for FDA, and put into this format, then reviewed by
FDA personnel. I think that the only way for FDA experts to get
an accurate idea of vaccine reactions is for them to review more
detailed reports, contact treating physicians directly, or investigate
sufficient numbers of actual cases. Currently they are required
only to investigate deaths.
The Defense Department did initiate its own study to resolve the
question of long-term safety of the vaccine in September of 1998
amidst all of the controversy. This was done at Tripler Army Medical
Center and 603 medical personnel were enrolled in an observational
study. These data were presented in April 1999 to Congress. 43%
of vaccine recipients had mild systemic reactions, and 5% had moderate
or severe systemic reactions after one of the first four vaccine
doses
This is a later GAO report to Congress, from July of 1999. It shows
that over 60% of males reported muscle soreness after each vaccination
and 60-80% of females reported the same thing. It shows that 2-5%
of males and 4-14% of females sought medical attention after one
of their first three vaccinations, and that 1-2% of males, but 4-5%
of females missed at least one shift of work after receiving a vaccine
dose. This vaccine causes adverse reactions in females at three
times the rate of males. However, followup information on this study
has not been released, so even though the Defense Department knows
what happened to these 603 people, Congress and the rest of us have
no information.about any persisting medical problems, which was
the question this study was designed to resolve.
In March 2000, at the request of the Defense Department, an Institute
of Medicine Committee investigating Gulf War Illness exposures reported
on the evidence for safety of the anthrax vaccine. They said, "The
Committee concludes that in the peer reviewed literature there is
inadequate, insufficient evidence to determine whether an association
does or does not exist between anthrax vaccination and long term
adverse health outcomes. This finding means that the evidence reviewed
by the committee is of insufficient quality, consistency or statistical
power to permit a conclusion regarding the presence or absence of
an association between the vaccine and a health outcome in humans."
Does vaccination of troops against biological
warfare agents even make sense strategically? This slide
from DARPA, the military's Defense Advanced Research Projects Agency,
lists over 65 known biological warfare agents, which are naturally
occurring. In addition, there are an infinite number of microorganisms
that may be created using genetic engineering. There are less than
10 vaccines effective against these agents. It takes an estimated
ten years, once one is aware of a microbial pathogen, to develop
an effective and safe vaccine against it.
The fact that we did not have an effective and safe anthrax vaccine
at the time of the Gulf War, and now 10 years later we still do
not have one, makes this perfectly clear. Furthermore, if we vaccinate
against anthrax, an enemy can just pick a different microorganism
to use. If an enemy genetically engineers a new virulent organism,
we will not even be able to begin developing a vaccine against it
until after it has presented itself -- in other words, after if
has been used. For these simple reasons, the use of vaccines against
the threat of biological warfare will never provide an effective
defense.
Dr. Ken Alibek, formerly the number two man in the Soviet Union’s
biological warfare program, has made this perfectly clear. "We
need to stop deceiving people that vaccines are the most effective
protection and start developing new therapeutic and preventive approaches
and means based on a broad spectrum protection."
How has the FDA responded to the question of vaccines for the biological
warfare threat? They have bought into the Defense Department’s
plan completely. In fact, FDA itself is helping to develop newer
vaccines against anthrax and other threat agents.
This new DNA plasmid encoding anthrax vaccine was developed at
the Center for Biologics Evaluation and Research, FDA’s center
for vaccine oversight. How can FDA provide proper oversight for
vaccines developed by its own staff? Shouldn't FDA's scientists
be helping the Defense Department to understand that vaccines are
not "the answer", rather than helping them stitch together
the emperor's new clothes?
Katherine Zoon, the Director of the FDA's CBER, the woman in charge
of vaccine oversight for every vaccine used in the United States,
has served on an Advisory Board for Biological Warfare for DARPA
and has advocated rapid approval of new biological warfare vaccines.
In this recently published article, she implies that the FDA review
process may be limited to only six months for such products. She
also says, "After these vaccines are licensed and administered,
the safety and adverse reactions of these vaccines should be assessed."
Ignoring Federal law, Dr. Zoon is suggesting that biowarfare vaccines
be licensed and used on humans and only afterwards should their
safety profile be ascertained. We have already learned that for
the current anthrax vaccine, post marketing surveillance is essentially
limited to VAERS reporting, and VAERS reporting is close to useless.
Should the military be given carte blanche to field biowarfare vaccines
and then determine whether they cause adverse reactions? Clearly,
if the case of anthrax vaccine is any example, the military will
do their best to prevent meaningful oversight and cover up adverse
reactions.
Dr. Katherine Zoon, Director of the Center for Biologics Evaluation
and Research at FDA, who is in charge of assuring that federal laws
are followed and that public health is protected with respect to
vaccines, has forgotten where her primary responsibilities lie.
For advocating that vaccines be administered
before their safety and adverse reactions are known she should immediately
lose her job.
The FDA has focused more on assisting the Defense Department,
than in assuring the public health. It is critical that FDA’s
priorities be immediately turned around, or the repercussions will
have grave effects on the health of both our military and civilians
of the United States.
Originally posted on the Anthrax
Vaccine Home Page http://www.anthraxvaccine.org/
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